What is the role of insulin in the management of Hyperosmolar Hyperglycemic State (HHS) in older adults with type 2 diabetes and impaired renal function?

Insulin Management in Hyperosmolar Hyperglycemic State (HHS)

Timing of Insulin Initiation is Critical

In HHS, insulin should be withheld initially and only started once the serum osmolality stops declining with intravenous fluid replacement alone, unless significant ketonaemia is present. 1, 2

This approach differs fundamentally from diabetic ketoacidosis (DKA) management and represents the most important distinction in HHS treatment.

Why Delay Insulin in HHS?

• Fluid replacement alone causes blood glucose to fall in HHS without requiring insulin, as rehydration restores glomerular filtration and allows glucose excretion 1, 2
• Early insulin administration (before adequate fluid resuscitation) may be detrimental and can precipitate dangerous complications 2
• The goal is to achieve a gradual decline in osmolality of 3.0-8.0 mOsm/kg/h to minimize the risk of neurological complications including central pontine myelinolysis and cerebral edema 1, 2
• Rapid osmolality changes during treatment may precipitate central pontine myelinolysis, a devastating complication with higher risk in elderly patients 2

When to Start Insulin in HHS

Commence fixed-rate intravenous insulin infusion (FRIII) only when:

• Blood glucose stops falling with IV fluid replacement alone 1, 2
• Exception: If ketonaemia is present (≥3.0 mmol/L), start insulin immediately alongside fluids as this indicates mixed DKA/HHS 1

Insulin Dosing Protocol

• Administer 10-15 units of regular human insulin as an intravenous bolus 3
• Follow with continuous infusion at 0.1 units/kg/hour 3
• Once blood glucose approaches 10-15 mmol/L (180-270 mg/dL) in the first 24 hours, add 5% or 10% dextrose infusion and reduce insulin infusion rate 1, 3
• Target blood glucose of 10-15 mmol/L in the first 24 hours, not normoglycemia 1

Critical Pitfalls to Avoid in Elderly Patients with HHS

• Never start insulin before adequate fluid resuscitation unless ketonaemia is present, as this can worsen hyperosmolality and precipitate neurological complications 2
• Do not aim for rapid glucose correction - the goal is gradual osmolality reduction over 24-72 hours, not immediate normoglycemia 1, 2
• Elderly patients with impaired renal function have reduced insulin clearance, increasing hypoglycemia risk once insulin is started 4, 5
• Monitor for hypoglycemia vigilantly as elderly patients fail to perceive neuroglycopenic and autonomic hypoglycemic symptoms 4
• Avoid aggressive insulin dosing in elderly patients with renal impairment - consider reducing the standard 0.1 units/kg/hour infusion rate 4

Fluid Resuscitation Takes Priority

• Administer 0.9% sodium chloride intravenously as the principal fluid to restore circulating volume 1, 2
• Fluid losses in HHS are typically 100-220 ml/kg, requiring aggressive replacement with caution in elderly patients who may have heart failure 1, 5
• An initial rise in sodium level is expected and normal - this is not an indication for hypotonic fluids 2
• Switch to 0.45% NaCl only after vital signs stabilize 3

Resolution Criteria for HHS

• Osmolality <300 mOsm/kg 1
• Hypovolemia corrected (urine output ≥0.5 ml/kg/h) 1
• Cognitive status returned to pre-morbid state 1
• Blood glucose <15 mmol/L 1

Special Considerations for Elderly with Renal Impairment

• Reduced glomerular filtration rate in elderly patients impairs glucose excretion, contributing to HHS development 5
• Decreased renal insulin degradation and excretion prolongs insulin action and increases hypoglycemia risk once insulin therapy begins 4
• Renal failure is a predictive marker for hypoglycemia in elderly hospitalized patients 4
• Following HHS resolution, many elderly patients will not require long-term insulin therapy and can be managed with diet or oral agents 3